2,2-difluorocyclopropyl derivatives

ABSTRACT

2,2-Difluorocyclopropyl derivatives of the formula ##STR1## in which R represents alkyl, optionally substituted aryl or optionally substituted aralkyl and 
     X represents hydroxymethyl, 2-hydroxyethyl, isocyanato, amino, amino hydrohalide or a radical of the formula --CO--R 1 , where 
     R 1  represents hydrogen, hydroxyl, alkoxy, alkyl, halogen or amino, 
     are intermediates for fungicides.

This application is a continuation of application Ser. No. 378,545,filed 7/11/89, now abandoned.

The present invention relates to novel 2,2-difluorocyclopropylderivatives, several processes for the preparation thereof, and the usethereof as intermediates for the synthesis of compounds havingfungicidal activity.

Certain cyclopropyl derivatives and the use thereof as intermediates forthe preparation of azolyl derivatives having fungicidal properties havealready been disclosed (cf. EP-OS (European Published Specification)0,040,345 and EP-OS (European Published Specification) 0,180,136). Thus,1-(4-chlorophenoxy)-2-cyclopropyl-3-(1,2,4-triazol-1-yl)-propan-2-ol,1-(4-chlorophenyl)-1-(1-chloro-cycloprop-1-yl)-2-(1,2,4-triazol-1-yl)-ethan-1-oland1-(4-chlorophenyl)-1-[1-(2,4-dichlorophenoxy-cycloprop-1-yl]-2-(1,2,4-triazol-1-yl)-ethan-1-olcan be prepared from corresponding cyclopropyl derivatives and used forcombating fungi. The activity of these substances is good, but leavessomething to be desired in some cases when low application rates areused.

Novel 2,2-difluorocyclopropyl derivatives of the formula ##STR2## inwhich R represents alkyl, optionally substituted aryl or optionallysubstituted aralkyl and

X represents hydroxymethyl, 2-hydroxyethyl, isocyanato, amino, aminohydrohalide or the radical of the formula --CO--R¹, where

R¹ represents hydrogen, hydroxyl, alkoxy, alkyl, halogen or amino,

have now been found.

Furthermore, it has been found that 2,2-difluorocyclopropyl derivativesof the formula (I) can be prepared by a process in which

a) vinylcyclopropane derivatives of the formula ##STR3## in which R hasthe abovementioned meaning, are reacted either

α) with a strong oxidant in the presence of a diluent, or

β) with ozone in the presence of a diluent and with a reducing agent, or

γ) initially in step 1 with diborane in the presence of a diluent andthe resulting product is then reacted in step 2 with a strong oxidant inthe presence of a diluent,

b) 2,2-difluorocyclopropyl derivatives of the formula ##STR4## in whichR has the abovementioned meaning, are reacted either

α) with a halogenating agent, if appropriate in the presence of adiluent, or

β) with a complex hydride in the presence of a diluent, or

γ) with organometallic compounds of the formula

    R.sup.2 --Li                                               (III)

in which

R² represents alkyl, in the presence of a diluent, or

c) 2,2-difluorocyclopropyl derivatives of the formula ##STR5## in whichR has the abovementioned meaning and Hal stands for halogen, are reactedeither

α) with an azide group-transferring reagent in the presence of a diluentand the resultant compounds of the formula ##STR6## in which R has theabovementioned meaning, are thermally decomposed in the presence of adiluent, or

β) with alcohols of the formula

    R.sup.3 --OH                                               (IV)

in which

R³ represents alkyl,

if appropriate in the presence of a catalyst and if appropriate in thepresence of a diluent, or

δ) with ammonia, if appropriate in the presence of a diluent, or

d) 2,2-difluorocyclopropyl derivatives of the formula ##STR7## in whichR has the abovementioned meaning, are reacted with hydrohalic acid inthe presence of a diluent and if appropriate the resultant compounds ofthe formula ##STR8## in which R has the abovementioned meaning and

Hal' represents halogen, are reacted with bases, if appropriate in thepresence of a diluent.

Finally, it has been found that the novel 2,2-difluorocyclopropylderivatives of the formula (I) can be very easily used as intermediatesfor the preparation of 2,2-difluorocyclopropyl-hydroxyethyl-azoleshaving fungicidal activity.

Surprisingly, the 2,2-difluorocyclopropyl-hydroxyethyl-azoles which canbe prepared from the 2,2-difluorocyclopropyl derivatives of the formula(I) according to the invention show a better fungicidal activity than1-(4-chlorophenoxy)-2-cyclopropyl-3-(1,2,4-triazol-1-yl)propan-2-ol,1-(4-chlorophenyl)-1-(1-chloro-cycloprop-1-yl)-2-(1,2,4-triazol-1-yl)-ethan-1-oland1-(4-chlorophenyl)-1-[1-(2,4-dichlorophenoxy)-cycloprop-1-yl]-2(1,2,4-triazol-1-yl)-ethan-1-ol,which are previously known active compounds of similar structure and thesame type of action.

Formula (I) provides a general definition of the 2,2-difluorocyclopropylderivatives according to the invention. Preferred compounds are those inwhich

R represents alkyl having 1 to 4 carbon atoms or phenyl which can bemonosubstituted to trisubstituted by identical or different substituentsfrom the series comprising halogen, alkyl having 1 to 4 carbon atoms,alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms,halogenoalkyl having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkoxy having 1 or 2 carbon atoms and 1to 5 identical or different halogen atoms, halogenoalkylthio having 1 or2 carbon atoms and 1 to 5 identical or different halogen atoms,alkoximinomethyl having 1 to 4 carbon atoms in the alkyl moiety and 1 to4 carbon atoms in the alkoxy moiety, phenoximinoalkyl which has 1 to 4carbon atoms in the alkyl moiety and which is optionally substituted byalkyl having 1 or 2 carbon atoms and/or halogen, phenyl which isoptionally substituted by alkyl having 1 or 2 carbon atoms and/orhalogen, and/or phenoxy which is optionally substituted by alkyl having1 or 2 carbon atoms and/or halogen, or

R represents benzyl which can be monosubstituted to trisubstituted inthe phenyl moiety by identical or different substituents from the seriescomprising halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkylhaving 1 or 2 carbon atoms and 1 to 5 identical or different halogenatoms, halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, alkoximinoalkyl having1 to 4 carbon atoms in the alkyl moiety and 1 to 4 carbon atoms in thealkoxy moiety, phenoximinoalkyl which has 1 to 4 carbon atoms in thealkyl moiety and which is optionally substituted by alkyl having 1 or 2carbon atoms and/or halogen, phenyl which is optionally substituted byalkyl having 1 or 2 carbon atoms and/or halogen, or phenoxy which isoptionally substituted by alkyl having 1 or 2 carbon atoms and/orhalogen, and

X represents hydroxymethyl, 2-hydroxyethyl, isocyanato, amino, aminohydrochloride, hydrobromide or hydroiodide, or represents the radical ofthe formula --COR¹, where

R¹ represents hydrogen, hydroxyl, alkoxy having 1 to 6 carbon atoms,alkyl having 1 to 6 carbon atoms, chlorine, bromine, iodine or amino.

Particularly preferred 2,2-difluorocyclopropyl derivatives of theformula (I) are those in which

R represents methyl, ethyl, isopropyl, tert.-butyl, or represents phenylwhich is optionally monosubstituted or disubstituted by identical ordifferent substituents from the series comprising fluorine, chlorine ormethyl, or represents benzyl which can be monosubstituted ordisubstituted in the phenyl moiety by identical or differentsubstituents from the series comprising fluorine, chlorine and/ormethyl, and

X represents hydroxymethyl, 2-hydroxymethyl, isocyanato, amino, aminohydrochloride, hydrobromide or hydriodide, or represents the radical ofthe formula --CO--R¹, where

R¹ represents hydrogen, hydroxyl, alkoxy having 1 to 4 carbon atoms,alkyl having 1 to 4 carbon atoms, chlorine, bromine, iodine or amino.

Very particularly preferred 2,2-difluorocyclopropyl derivatives of theformula (I) are those in which

R represents methyl, ethyl, benzyl or phenyl which is optionallymonosubstituted or disubstituted by fluorine, chlorine and/or methyl,and

X represents hydroxymethyl, 2-hydroxyethyl, isocyanato, amino, aminohydrochloride, hydrobromide or hydroiodide, or represents the radical ofthe formula --CO--R¹, where

R¹ represents hydrogen, hydroxyl, methoxy, ethoxy, isopropoxy, n-butoxy,methyl, ethyl, isopropyl, n-butyl, chlorine, bromine, iodine or amino.

If, for example, 2,2-difluoro-1-methyl-1-vinylcyclopropane is used asstarting substance and potassium permanganate as oxidant, the course ofprocess (a, variant α) according to the invention can be illustrated bythe following equation: ##STR9##

If 2,2-difluoro-1-methyl-1-vinyl-cyclopropane is used as startingsubstance and ozone as reactant, the course of process (a, variant β)can be illustrated by the following equation: ##STR10##

If 2,2-difluoro-1-methyl-1-vinyl-cyclopropane is used as startingsubstance and diborane and subsequently hydrogen peroxide are used asreactants, the course of process (a, variant γ) according to theinvention can be illustrated by the following equation: ##STR11##

If 2,2-difluoro-1-methyl-1-cyclopropanecarboxylic acid is used asstarting substance and thionyl chloride as halogenating agent, thecourse of process (b, variant α) according to the invention can beillustrated by the following equation: ##STR12##

If 2,2-difluoro-1-methyl-1-cyclopropanecarboxylic acid is used asstarting substance and lithium aluminum hydride is used as complexhydride, the course of process (b, variant β) according to the inventioncan be illustrated by the following equation: ##STR13##

If 2,2-difluoro-1-methyl-cyclopropanecarboxylic acid is used as startingsubstance and methyllithium as organometallic compound, the course ofprocess (b, variant γ) according to the invention can be illustrated bythe following equation: ##STR14##

If 2,2-difluoro-1-methyl-1-cyclopropanecarboxylic acid is used asstarting substance and trimethylsilyl azide as reactant, the course ofprocess (c, variant α) according to the invention can be illustrated bythe following equation: ##STR15##

If 2,2-difluoro-1-methyl-cyclopropane-carbonyl chloride is used asstarting substance and ethanol as reactant, the course of process (c,variant β) according to the invention can be illustrated by thefollowing equation: ##STR16##

If 2,2-difluoro-1-methyl-1-cyclopropane-carbonyl chloride is used asstarting substance and ammonia as reactant, the course of process (c,variant α) according to the invention can be illustrated by thefollowing equation: ##STR17##

If 2,2-difluoro-1-methyl-cyclopropyl isocyanate is used as startingsubstance and concentrated hydrochloric acid as reactant, the course ofprocess (d) according to the invention can be illustrated by thefollowing equation: ##STR18##

Formula (II) provides a general definition of the vinylcyclopropanederivatives required as starting substances for carrying out process (a)according to the invention. In this formula, R preferably stands forthose radicals which have already been mentioned in connection with thedescription of the substances of the formula (I) according to theinvention as being preferred for R.

The vinylcyclopropane derivatives of the formula (II) are known or canbe prepared by processes which are known in principle (cf Liebigs Ann.Chem. 710, 17-35 (1967) and Chem. Ber. 109, 2351-2369 (1976)).

Suitable strong oxidants for carrying out process (a, variant α)according to the invention are all those oxidants which are suitable forsplitting olefinic double bonds. Potassium permanganate can preferablybe used.

Possible diluents for carrying out variant α of process (a) according tothe invention are all solvents which are customary for reactions of thistype. Water can preferably be used.

When carrying out process (a, variant α) according to the invention, thetemperatures can be varied within a certain range. In general, theprocess is carried out at temperatures between 0° C. and 60° C.,preferably between 10° C. and 50° C.

Process (a, variant α) according to the invention is generally carriedout under atmospheric pressure, as are the other processes described inthis application. However, it is in each case also possible to carry outthe reaction under increased or reduced pressure.

When carrying out process (a, variant α) according to the invention, 2to 3 moles of strong oxidant are generally employed per mole ofvinylcyclopropane derivative of the formula (II). Working up is carriedout by customary methods.

Possible reducing agents for carrying out process (a, variant β)according to the invention are all reducing agents which are customaryfor ozonolyses of this type. Triphenylphosphine, trimethyl phosphite,dimethyl sulphide and hydrogen in the presence of a catalyst canpreferably be used.

Suitable diluents for carrying out process (a, variant β) according tothe invention are all solvents which are customary for ozonolyses ofthis type. Alcohols, such as methanol or ethanol, can preferably beused.

When carrying out process (a, variant β) according to the invention, thereaction temperatures can be varied within a certain range. In general,the process is carried out at temperatures between -80° C. and -20° C.,preferably between -80° C. and -40° C.

When carrying out process (a, variant β) according to the invention,ozone is passed through the reaction mixture until the reaction iscomplete. Working up is carried out by customary methods. In general, aprocedure is followed in which an excess of reducing agent is added tothe reaction mixture and stirring is initially continued with cooling.After the reaction mixture has come to room temperature, it is dilutedwith water and extracted using an organic solvent which is sparinglysoluble in water, and the combined organic phases are dried anddistilled.

The diborane required for carrying out process (a, variant γ) accordingto the invention is generally freshly prepared, for example by reactingboron trifluoride etherate with sodium borohydride in the presence of aninert organic diluent, such as, for example, diglyme. The resultantdiborane is directly reacted further.

Possible diluents for carrying out step one of process (a, variant γ)according to the invention are all inert organic solvents which arecustomary for reactions of this type. Ethers, such as diethyl ether,dioxane or tetrahydrofuran, can preferably be used.

If appropriate, step one of process (a, variant γ) according to theinvention is carried out under a protective gas atmosphere, preferablyunder nitrogen or under argon.

When carrying out process (a, variant γ) according to the invention, thereaction temperatures can be varied within a certain range both in step1 and in step 2. In general, the reaction is carried out at temperaturesbetween 0° C. and 60° C., preferably between 10° C. and 50° C.

When carrying out step 1 of process (a, variant γ), a stoichiometricamount or, even a subequivalent amount, of diborane is employed per moleof vinylcyclopropane derivative of the formula (II). When the reactionis complete, a procedure is generally followed in which excessvinylcyclopropane derivative of the formula (II) and solvent are removedunder reduced pressure. The residue is directly reacted further.

Possible diluents for carrying out step 2 of process (a, variant γ)according to the invention are likewise preferably ethers, such asdiethyl ether, tetrahydrofuran and dioxane.

Possible strong oxidants for carrying out step 2 of process (a, variantγ) according to the invention are all customary strong oxidants.Hydrogen peroxide can preferably be used.

When carrying out process (a, variant γ) according to the invention,hydrogen peroxide can be employed in the form of dilute aqueoussolutions and in the presence of aqueous alkali hydroxide solution, suchas, for example, aqueous sodium hydroxide solution.

When carrying out step 2 of process (a, variant γ) according to theinvention, a procedure is generally followed in which the productobtained in step 1 taken up in a solvent and an excess of each aqueousalkali hydroxide solution and aqueous hydrogen peroxide solution or asimilar oxidant is added in succession. Working up is generally carriedout by extracting the mixture several times using an organic solventwhich is sparingly soluble in water, and the combined organic phases aredried and distilled under reduced pressure.

Formula (Ia) provides a general definition of the2,2-difluorocyclopropyl derivatives required as starting substances forcarrying out process (b) according to the invention. In this formula, Rpreferably has those meanings which have already been mentioned inconnection with the description of the substances of the formula (I)according to the invention as being preferred for this radical.

The 2,2-difluorocyclopropyl derivatives of the formula (Ia) can beprepared by process (a, variant α) according to the invention.

Possible halogenating agents for carrying out process (b, variant α)according to the invention are all those substances which are suitablefor converting acids to acid halides. Thionyl chloride, sulphurylchloride, phosphorus trichloride, thionyl bromide and sulphuryl bromidecan preferably be used. The acid fluorides and acid iodides can beprepared from the corresponding bromides or chlorides by customarymethods.

Suitable diluents for carrying out process (b, variant α) according tothe invention are all inert organic solvents which are customary forreactions of this type. Preferably, the particular halogenating agent issimultaneously used as diluent.

When carrying out process (b, variant α) according to the invention, thereaction temperatures can be varied within a relatively wide range. Ingeneral, the process is carried out at temperatures between 0° C. and150° C., preferably between 20° C. and 80° C.

When carrying out process (b, variant α) according to the invention, 1to 2 equivalents, or alternatively a relatively large excess, ofhalogenating agent is employed per mole of 2,2-difluorocyclopropylderivative of the formula (Ia). Working up is carried out by customarymethods. In order to prepare acid iodides, acid bromides are reactedwith potassium iodide; while acid fluorides are accessible from otheracid halides by reaction with fluorides, such as, for example, sodiumfluoride, potassium fluoride, caesium fluoride or ammonium fluoride, orby reaction with hydrofluoric acid.

A suitable complex hydride for the preparation of process (b, variant β)according to the invention is preferably lithium aluminum hydride.

Possible diluents for carrying out process (b, variant β) according tothe invention are preferably ethers, such as diethyl ether, dioxane ortetrahydrofuran.

When carrying out process (b, variant β) according to the invention, thereaction temperatures can be varied within a relatively wide range. Ingeneral, the process is carried out at temperatures between -10° C. and+100° C., preferably between 10° C. and 70° C.

When carrying out process (b, variant β) according to the invention, anexcess of complex hydride is generally employed per mole of2,2-difluorocyclopropyl derivative of the formula (Ia). Working up iscarried out by customary methods. In general, a procedure is followed inwhich mild hydrolysis is carried out by adding water and diluteinorganic acid to the mixture and then extracting using a solvent, andthe combined organic phases are dried and distilled.

Formula (III) provides a general definition of the organometalliccompounds required as reactants for carrying out process (b, variant γ)according to the invention. In this formula, R² preferably representsalkyl having 1 to 6 carbon atoms.

The organometallic compounds of the formula (III) are generally knowncompounds of organic chemistry.

Possible diluents for carrying out process (b, variant γ) according tothe invention are all inert organic solvents customary for reactions ofthis type. Ethers, such as diethyl ether, dioxane or tetrahydrofuran canpreferably be used.

When carrying out process (b, variant γ) according to the invention, thereaction temperatures can be varied within a relatively wide range. Ingeneral, the process is carried out at temperatures between -100° C. and+50° C., preferably between -78° C. and 0° C.

Process (b, variant γ) is carried out under a protective gas atmosphere,such as, for example, under argon or nitrogen.

When carrying out process (b, variant γ) according to the invention, 1.5to 3.0 moles, preferably 2.0 moles, of organometallic compound of theformula (III) are generally employed per mole of 2,2-difluorocyclopropylderivative of the formula (Ia). Working up is carried out by customarymethods. In general, a procedure is followed in which the reactionmixture is poured onto ice and inorganic acid, the organic phase isseparated off, the aqueous phase is extracted using an organic solventwhich is almost immiscible with water, and the combined organic phasesare dried and distilled.

Formula (Ib) provides a general definition of the2,2-difluorocyclopropyl derivatives required as starting substances forcarrying out process (c, variant α) according to the invention. In thisformula, R preferably has those meanings which have already beenmentioned in connection with the description of the substances of theformula (I) according to the invention as being preferred for theradical R. Hal preferably stands for fluorine, chlorine or bromine.

The 2,2-difluorocyclopropyl derivatives of the formula (Ib) can beprepared by process (b, variant α) according to the invention.

Suitable reagents for transferring azide groups when process (c, variantα) according to the invention is carried out are all substances whichare customary for reactions of this type. Trimethylsilyl azide canpreferably be used.

Possible diluents for carrying out process (c, variant α) according tothe invention are all inert organic solvents which are customary forreactions of this type, both for the preparation of the compounds of theformula (Ic) and for their thermal decomposition. Aliphatic or aromatichydrocarbons, such as hexane, benzene, xylene or toluene can preferablybe used.

When carrying out process (c, variant α) according to the invention, thereaction temperatures can be varied within a relatively wide range. Ingeneral, the compounds of the formula (Ic) are prepared at temperaturesbetween 0° C. and 30° C., preferably between 5° C. and 25° C. Thesubsequent thermal decomposition of the compounds of the formula (Ic) isgenerally carried out between 20° C. and 120° C., preferably between 25°C. and 100° C.

When carrying out process (c, variant α) according to the invention, 1to 1.5 moles of an azide group-transferring reagent are preferablyemployed per mole of 2,2-difluorocyclopropyl derivative of the formula(Ib). The product of the formula (Ic), which is formed as anintermediate, is thermally decomposed without isolation by slowlyincreasing the temperature of the reaction mixture. Subsequent workingup is carried out by customary methods. In general, a procedure isfollowed in which the reaction mixture is subjected to fractionaldistillation.

Formula (IV) provides a general definition of the alcohols required asreactants for carrying out process (c, variant β) according to theinvention. In this formula, R³ preferably represents alkyl having 1 to 6carbon atoms.

The alcohols of the formula (IV) are generally known compounds oforganic chemistry.

Possible catalysts for carrying out process (c, variant β) according tothe invention are all reaction accelerators which are customary for thepreparation of esters from acids or acid halides. Inorganic acids, suchas sulphuric acid, and also strong organic acids, such asp-toluenesulphonic acid, can preferably be used. Inorganic bases, suchas sodium hydroxide, and also organic bases, such as pyridine ortertiary amines, can likewise be used.

Suitable diluents for carrying out process (c, variant β) according tothe invention are all organic solvents which are customary for reactionsof this type. Preferably, the alcohol of the formula (IV), employed inexcess, also acts as solvent.

When carrying out process (c, variant β) according to the invention, thereaction temperatures can be varied within a relatively wide range. Ingeneral, the process is carried out at temperatures between 0° C. and150° C., preferably between 20° C. and 140° C.

When carrying out process (c, variant β) according to the invention, 1to 3 moles, or a relatively large excess, of alcohol of the formula(IV), and also a catalytic amount of reaction accelerator are employedper mole of 2,2-difluorocyclopropyl derivative of the formula (Ib).Working up is carried out by customary methods.

Possible diluents for carrying out process (c, variant γ) according tothe invention are all inert organic solvents which are customary forreactions of this type. Ethers, such as diethyl ether, dioxane andtetrahydrofuran can preferably be used.

When carrying out process (c, variant γ) according to the invention, thereaction temperatures can also be varied within a relatively wide range.In general, the process is carried out at temperatures between 0° C. and60° C., preferably between 10° C. and 40° C.

When carrying out process (c, variant γ) according to the invention,2,2-difluorocyclopropyl derivatives of the formula (Ib) are reacted withan excess of ammonia. Expediently, a procedure is followed in which the2,2-difluorocyclopropyl derivative of the formula (Ib) is initiallyintroduced as a solution, and gaseous ammonia is passed in tosaturation. Working up is carried out by customary methods. In general,a procedure is followed in which the reaction mixture is concentratedunder reduced pressure and the product which remains in this process isstirred with water, filtered off with suction and dried.

Formula (Id) provides a general definition of the2,2-difluorocyclopropyl derivatives required as starting substances forcarrying out process (d) according to the invention. In this formula, Rpreferably has those meanings which have already been mentioned inconnection with the description of the substances of the formula (I)according to the invention as being preferred for the radical R.

The 2,2-difluorocyclopropyl derivatives of the formula (Id) can beprepared by process (c, variant α) according to the invention.

Suitable hydrohalic acids for carrying out process (d) according to theinvention are preferably hydrochloric acid, hydrobromic acid orhydriodic acid in the form of their aqueous solutions.

Possible diluents for carrying out process (d) according to theinvention are all organic solvents which are customary for reactions ofthis type. Aliphatic or aromatic hydrocarbons, such as hexane, benzene,toluene or xylene can preferably be used.

When carrying out process (d) according to the invention, the reactiontemperatures can be varied within a certain range. In general, theprocess is carried out at temperatures between 0° C. and 150° C.,preferably between 10° C. and 100° C.

When carrying out process (d) according to the invention, 1 to 5 molesof hydrohalic acid in the form of an aqueous solution are preferablyemployed per mole of 2,2-difluorocyclopropyl derivative of the formula(Id). Working up is carried out by customary methods. In general, aprocedure is followed in which the reaction mixture is concentratedunder reduced pressure and, if appropriate, the residue remaining ispurified by customary methods.

If it is intended to prepare the free amines when carrying out process(d) according to the invention, bases are added to the compounds of theformula (Ie), if appropriate in the presence of a diluent. Possiblebases for this process preferably are aqueous alkali hydroxidesolutions, such as sodium hydroxide solution or potassium hydroxidesolution. Suitable solvents are inert organic solvents or water.

When preparing the free amines by process (d) according to theinvention, the reaction temperatures can be varied within a relativelywide range. In general, the process is carried out at temperaturesbetween -10° C. and +50° C., preferably between 0° C. and +30° C.

When preparing the free amines by process (d) according to theinvention, the compounds of the formula (Ie) are reacted with an excessof base. Working up is carried out by customary methods. In general, aprocedure is followed in which the reaction mixture is extracted with anorganic solvent which is almost immiscible with water, if appropriatefollowing previous reaction with water, the combined organic phases aredried and concentrated, and the residue remaining is distilled.

The 2,2-difluorocyclopropyl derivatives of the formula (I) according tothe invention are suitable as intermediates for the synthesis of plantprotection agents, in particular for the preparation of substanceshaving fungicidal activity.

Thus, for example, 2,2-difluorocyclopropylhydroxyethyl-triazoles of theformula ##STR19## in which R has the abovementioned meaning,

Ar represents optionally substituted aryl and

Y represents the groups --OCH₂ --, --SCH₂ --, --CH₂ --CH₂ -- or--CH═CH--,

are prepared by a process in which

e) methyl cyclopropyl ketones of the formula ##STR20## in which R hasthe abovementioned meaning,

are reacted with chlorinating agents or brominating agents, such assulphuryl chloride sulphuryl bromide or bromine, in the presence of adiluent, such as methylene chloride, chloroform or carbon tetrachloride,at temperatures between -10° C. and +60° C., preferably between 0° C.and 40° C., and the resultant halogenoketones of the formula ##STR21##in which R has the abovementioned meaning and

Hal" represents chlorine or bromine,

are reacted with compounds of the formula

    Ar--Z--H                                                   (VII)

in which

Ar has the abovementioned meaning and

Z represents oxygen or sulphur,

in the presence of an acid-binding agent and if appropriate in thepresence of a diluent at temperatures between 0° C. and 150° C.,preferably between 20° C. and 130° C., and the resultant cyclopropylketones of the formula ##STR22## in which Ar, R and Z have theabovementioned meanings, are reacted either

α) with dimethyloxosulphonium methylide of the formula ##STR23## or β)with dimethylsulphonium methylide of the formula ##STR24## in thepresence of a diluent at temperatures between 0° C. and 100° C.,preferably between 10° C. and 60° C., and, finally, the resultantoxiranes of the formula ##STR25## in which Ar, R and Z have theabovementioned meanings, are reacted with 1,2,4-triazole of the formula##STR26## in the presence of an acid-binding agent and in the presenceof a diluent at temperatures between 0° C. and 200° C., preferablybetween 50° C. and 150° C., or in which

f) methyl cyclopropyl ketones of the formula ##STR27## in which R hasthe abovementioned meaning are reacted with aldehydes of the formula

    Ar--CHO                                                    (XIII)

in which

Ar has the abovementioned meaning, in the presence of a catalyst, suchas sodium hydroxide or potassium hydroxide, and also in the presence ofa diluent, such as methanol, ethanol, isopropanol, n-butanol ortert.-butanol, at temperatures between 0° C. and 100° C., preferablybetween 10° C. and 80° C., and, if appropriate, the resultantcyclopropyl ketones of the formula ##STR28## in which R and Ar have theabovementioned meanings,

are hydrogenated with hydrogen in the presence of a hydrogenationcatalyst and in the presence of a diluent, and, finally, the cyclopropylketones thus obtained, of the formula ##STR29## in which Ar and R havethe abovementioned meanings and

Z¹ stands for the groups --CH═CH-- or --CH₂ --CH₂ --, are reacted

α) with dimethyloxosulphonium methylide of the formula ##STR30## or β)with dimethylsulphonium methylide of the formula ##STR31## in thepresence of a diluent at temperatures between 0° C. and 100° C.,preferably between 10° C. and 60° C., and, finally, the resultantoxiranes of the formula ##STR32## in which Ar, R and Z¹ have theabovementioned meanings, are reacted with 1,2,4-triazole of the formula##STR33## in the presence of an acid-binding agent and in the presenceof a diluent at temperatures between 0° C. and 200° C., preferablybetween 50° C. and 150° C.

Furthermore, hydroxyalkinyl-azolyl derivatives of the formula ##STR34##in which Ar and R have the abovementioned meanings,

can be prepared by a process in which

g) 2,2-difluorocyclopropyl derivatives of the formula ##STR35## in whichR and Hal have the abovementioned meanings,

are reacted with acetyl derivatives of the formula

    Ar--C.tbd.CH                                               (XVIII)

in which

Ar has the abovementioned meaning,

in the presence of a catalyst, such as copper(I) bromide, and in thepresence of an acid-binding agent, such as sodium hydroxide or potassiumhydroxide, and in the presence of a diluent, such as toluene, attemperatures between 0° C. and 150° C., preferably between 20° C. and120° C., and the resultant cyclopropyl ketones of the formula ##STR36##in which Ar and R have the abovementioned meanings,

are reacted with dimethylsulphonium methylide of the formula ##STR37##in the presence of a diluent at temperatures between 0° C. and 100° C.,preferably between 10° C. and 60° C., and, finally, the resultantoxiranes of the formula ##STR38## in which Ar and R have theabovementioned meanings,

are reacted with 1,2,4-triazole of the formula ##STR39## in the presenceof an acid-binding agent and in the presence of a diluent attemperatures between 0° C. and 200° C., preferably between 50° C. and150° C.

The remaining 2,2-difluorocyclopropyl derivatives of the formula (I) canbe used in a corresponding manner as intermediates for the synthesis ofplant protection agents, in particular of substances having fungicidalactivity.

The 2,2-difluorocyclopropyl-hydroxyethyl-triazoles of the formula (V)and the hydroxalkinyl-azolyl derivatives of the formula (XVII) exhibit apowerful microbicidal action and can be employed as fungicides.

Fungicides in plant protection are employed for combatingPlasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes,Ascomycetes, Basidiomycetes and Deuteromycetes.

Some causative organisms of fungal and bacterial diseases which comeunder the generic names listed above may be mentioned as examples, butnot by way of limitation: Xanthomonas species, such as Xanthomonasoryzae; Pseudomonas species, such as Pseudomonas lachrymans; Erwiniaspecies, such as Erwinia amylovora; Pythium species, such as Pythiumultimum; Phytophthora species, such as Phytophthora infestans;Pseudoperonospora species, such as Pseudoperonospora humuli orPseudoperonospora cubense; Plasmopara species, such as Plasmoparaviticola; Peronospora species, such as Peronospora pisi or P. brassicae;Erysiphe species, such as Erysiphe graminis; Sphaerotheca species, suchas Sphaerotheca fuliginea; Podosphaera species, such as Podosphaeraleucotricha; Venturia species, such as Venturia inaequalis; Pyrenophoraspecies, such as Pyrenophora teres or P. graminea (conidia form:Drechslera, syn: Helminthosporium); Cochliobolus species, such asCochliobolus sativus (conidia form: Drechslera, syn: Helminthosporium);Uromyces species, such as Uromyces appendiculatus; Puccinia species,such as Puccinia recondita; Tilletia species, such as Tilletia caries;Ustilago species, such as Ustilago nuda or Ustilago avenae; Pelliculariaspecies, such as Pellicularia sasakii; Pyricularia species, such asPyricularia oryzae; Fusarium species, such as Fusarium culmorum;Botrytis species, such as Botrytis cinerea; Septoria species, such asSeptoria nodorum; Leptosphaeria species, such as Leptosphaeria nodorum;Cercospora species, such as Cercospora canescens; Alternaria species,such as Alternaria brassicae and Pseudocercosporella species, such asPseudocercosporella herpotrichoides.

The good toleration, by plants, of the active compounds, at theconcentrations required for combating plant diseases, permits treatmentof above-ground parts of plants, of vegetative propagation stock andseeds, and of the soil.

The active compounds of the formulae (V) and (XVII) are particularlysuitable for combating cereal diseases, such as Erysiphe graminis,Puccinia recondita, Cochliobolus sativus, Pyrenophora teres,Leptospaeria nodorum and barley mildew; furthermore rice diseases, suchas Pyricularia oryzae and Pellicularia sasakii; and also Venturiaspecies and cucumber mildew. Moreover, the substances have a very goodin vitro action.

The active compounds of the formulae (V) and (XVII) can be converted tothe customary formulations, such as solutions, emulsions, suspensions,powders, foams, pastes, granules, aerosols, very fine capsules inpolymeric substances and in coating compositions for seed, as well asULV formulations.

These formulations are produced in a known manner, for example by mixingthe active compounds with extenders, that is, liquid solvents, liquefiedgases under pressure, and/or solid carriers, optionally with the use ofsurface-active agents, that is, emulsifying agents and/or dispersingagents, and/or foam-forming agents. In the case of the use of water asan extender, organic solvents can, for example, also be used asauxiliary solvents. As liquid solvents, there are suitable in the main:aromatics, such as xylene, toluene or alkylnaphthalenes, chlorinatedaromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes,chloroethylenes or methylene chloride, aliphatic hydrocarbons, such ascyclohexane or paraffins, for example mineral oil fractions, alcohols,such as butanol or glycol as well as their ethers and esters, ketones,such as acetone, methyl ethyl ketone, methyl isobutyl ketone orcyclohexanone, strongly polar solvents, such as dimethylformamide anddimethyl sulphoxide, as well as water. By liquefied gaseous extenders orcarriers are meant liquids which are gaseous at normal temperature andunder normal pressure, for example aerosol propellants, such ashalogenated hydrocarbons as well as butane, propane, nitrogen and carbondioxide. As solid carriers there are suitable: for example groundnatural minerals, such as kaolins, clays, talc, chalk, quartz,attapulgite, montmorillonite or diatomaceous earth, and ground syntheticminerals, such as highly disperse silica, alumina and silicates. Assolid carriers for granules there are suitable: for example crushed andfractionated natural minerals such as calcite, marble, pumice, sepioliteand dolomite, as well as synthetic granules of inorganic and organicmeals, and granules of organic material such as sawdust, coconut shells,corn cobs and tobacco stalks. As emulsifying and/or foam-forming agentsthere are suitable: for example non-ionic and anionic emulsifiers, suchas polyoxyethylene fatty acid esters, polyoxyethylene fatty alcoholethers, for example alkylaryl polyglycol ethers, alkylsulphonates, alkylsulphates, arylsulphonates as well as albumin hydrolysis products. Asdispersing agents there are suitable: for example ligninsulphite wasteliquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, as well as naturalphospholipids, such as cephalins and lecithins, and syntheticphospholipids, can be used in the formulations. Other additives can bemineral and vegetable oils.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs and metal phthalocyaninedyestuffs, and trace nutrients such as salts of iron, manganese, boron,copper, cobalt, molybdenum and zinc.

The formulations in general contain between 0.1 and 95 per cent byweight of active compound, preferably between 0.5 and 90%.

The active compounds according to the invention can be present in theformulations as a mixture with other known active compounds, such asfungicides, insecticides, acaricides and herbicides, as well as inmixtures with fertilizers and growth regulators.

The active compounds can be used as such or in the form of theirformulations or the use forms prepared therefrom, such as ready-to-usesolutions, emulsifiable concentrates, emulsions, foams, suspensions,wettable powders, pastes, soluble powders, dusts and granules. They areused in the customary manner, for example by watering, spraying,atomizing, scattering, dusting, foaming, brushing on and the like. It isfurthermore possible to apply the active compounds by the ultra-lowvolume method or to inject the active compound formulation or the activecompound itself into the soil. The seeds of the plants can also betreated.

Depending on the manner of application, the application rates of activecompounds of the formulae (V) and (XVII) can be varied within arelatively wide range. Thus, in the treatment of parts of plants, theactive compound concentrations in the use forms are, in general, between1 and 0.0001% by weight, preferably between 0.5 and 0.001%. In thetreatment of seed, amounts of active compound of 0.001 to 50 g perkilogram of seed, preferably 0.01 to 10 g, are generally required. Inthe treatment of soil, active compound concentrations of 0.00001 to 0.1%by weight, preferably 0.0001 to 0.02% by weight, are required at theplace of action.

The preparation of the 2,2-difluorocyclopropyl derivatives of theformula (I) according to the invention and their use as intermediatesfor the synthesis of substances having fungicidal activity can be seenfrom the following examples.

PREPARATION EXAMPLES EXAMPLE 1 ##STR40##

2.3 kg (14.47 mol) of potassium permanganate are added in portions to840 g (7.12 mol) of 2,2-difluoro-1-methyl-1-vinyl-cyclopropane in 10 lof water. The mixture is stirred at room temperature for 36 hours, andmanganese dioxide is filtered off and rinsed thoroughly with water. Thefiltrate is acidified using concentrated hydrochloric acid and extractedusing dichloromethane. After the organic phase has been dried, thesolvent is removed under reduced pressure and the residue is distilled.

In this manner, 750 g (77% of theory) of2,2-difluoro-1-methylcyclopropanecarboxylic acid of melting point59°-61° C. are obtained.

EXAMPLE 2 ##STR41##

Ozone is passed into a stirred solution of 30 g (0.25 mol) of2,2-difluoro-1-methyl-1-vinyl-cyclopropane in 250 ml of methanol at -78°C. A solution of 50 g (0.4 mol) of trimethyl phosphite in 50 ml ofmethanol is then added dropwise, and stirring is continued for one hourat -78° C. The reaction mixture is subsequently warmed slowly to roomtemperature and then poured into water. The resulting mixture isextracted several times using diethyl ether, and the combined organicphases are dried and distilled under reduced pressure. In this manner,9.2 g (31% of theory) of2,2-difluoro-1-methyl-cyclopropane-carboxaldehyde are obtained in formof a liquid of boiling point 110°-112° C./200 torr.

EXAMPLE 3 ##STR42##

0.23 mol of diborane is produced from 6.7 g (0.18 mol) of sodiumborohydride and 33 g (0.23 mol) of boron trifluoride etherate in 130 mlof diglyme, and, with the aid of a stream of nitrogen, is passed into astirred solution of 30 g (0.25 mol) of2,2-difluoro-1-methyl-1-vinyl-cyclopropane in 300 ml of dry diethylether, at room temperature. The reaction mixture is stirred for one hourmore at room temperature and concentrated by stripping off the solventand the excess alkene under reduced pressure. The residue which remainsis taken up in 50 ml of diethyl ether, and 130 ml of 10% strengthaqueous sodium hydroxide solution are added. 134ml of a 30% strengthaqueous hydrogen peroxide solution are added dropwise to this mixture atroom temperature and with stirring. Stirring is continued for an hour atroom temperature, the mixture is extracted several times using diethylether, and the combined organic phases are dried and distilled underreduced pressure. In this manner, 13 g (55% of theory) of2-(2,2-difluoro-1-methyl-cyclopropyl)-ethanol are obtained in form of aliquid of boiling point 65°-67° C./20 torr.

EXAMPLE 4 ##STR43##

A mixture of 250 g (1.8 mol) of2,2-difluoro-1-methylcyclopropanecarboxylic acid and 700 ml of thionylchloride is heated slowly and with stirring in a distillation apparatus,with excess thionyl chloride distilling over first and the desiredproduct later. In this manner, 215 g (77% of theory) of2,2-difluoro-1-methyl-cyclopropane-carbonyl chloride are obtained inform of a liquid of boiling point 121°-122° C.

EXAMPLE 5 ##STR44##

A solution of 50 g (0.35 mol) of2,2-difluoro-1-methyl-cyclopropane-carboxylic acid in 50 ml of diethylether is added dropwise at room temperature to a stirred suspension of25 g (0.66 mol) of lithium aluminum hydride in 250 ml of dry diethylether. The mixture is subsequently refluxed for 4 hours, then allowed tocool to room temperature and carefully hydrolyzed by slowly adding waterand concentrated hydrochloric acid. The resultant mixture is extractedseveral times using diethyl ether, and the combined organic phases aredried and distilled through a Vigreux column. In this manner, 34.5 g(77% of theory) of 2,2-difluoro-1-methyl-cyclopropyl-methanol areobtained in form of a liquid of boiling point 136°-139° C.

EXAMPLE 6 ##STR45##

333 ml of a 1.5-molar methyllithium solution (0.5 mol) are addeddropwise at -78° C. under nitrogen to 34 g (0.25 mol) of2,2-difluoro-1-methylcyclopropanecarboxylic acid in 250 ml of drydiethyl ether, with stirring. Stirring is continued for one hour at -78°C., and the reaction solution is then warmed to 0° C. and poured onto500 g of ice and 50 ml of concentrated hydrochloric acid. The organicphase is separated off, and the aqueous phase is extracted using ether.The combined organic phases are dried over sodium sulphate, the solventis distilled off, and the product is distilled under slightly reducedpressure.

21 g (63% of theory) of 2,2-difluoro-1-methylcyclopropyl methyl ketoneof boiling point 58°-60° C./60 mbar are obtained.

EXAMPLE 7 ##STR46##

30.9 g (0.2 mol) of 2,2-difluoro-1-methyl-cyclopropane-carbonyl chlorideare added dropwise in the course of 10 minutes at 20° C. to a stirredsolution of 28 g (0.24 mol) of trimethylsilyl azide in 120 ml oftoluene. The temperature of the stirred reaction mixture is subsequentlyincreased to 90° C. in the course of 3 hours. Stirring is continueduntil the evolution of gas has ceased. The course of the reaction ismonitored by IR spectroscopy by occasionally determining the decrease ofthe azide band at 2130 cm⁻¹, by taking samples. When the reaction iscomplete, distillation is carried out. In this manner, 12.5 g (47% oftheory) of 2,2-difluoro-1-methyl-cyclopropyl isocyanate are obtained inform of a liquid of boiling point 95°-97° C.

EXAMPLE 8 ##STR47##

35 ml of ethanol are added dr©pwise at 20° C. to 15.45 g (0.1 mol) of2,2-difluoro-1-methyl-cyclopropanecarbonyl chloride, with stirring.After the addition of 2 drops of concentrated sulphuric acid, thereaction mixture is refluxed for another hour. Excess ethanol issubsequently distilled off, and the residue is dried and distilled underatmospheric pressure. In this manner, 14.2 g (87% of theory) of ethyl2,2-difluoro-1-methyl-cyclopropane-carboxylate are obtained in form of aliquid of boiling point 141°-143° C.

EXAMPLE 9 ##STR48##

Gaseous ammonia is passed for 90 minutes into a stirred solution of15.45 g (0.1 mol) of 2,2-difluoro-1-methyl-cyclopropane-carbonylchloride in 80 ml of dioxane at 20° to 30° C. The resultant suspensionis then evaporated to dryness under a waterpump vacuum. The residueremaining is stirred with 50 ml of water, filtered off with suction anddried. In this manner, 11 g (81% of theory) of2,2-difluoro-1-methyl-cyclopropyl-carboxamide in form of a solidsubstance of melting point 125°-127° C. are obtained.

EXAMPLE 10 ##STR49##

50 ml of concentrated hydrochloric acid are added to a solution of 13 g(0.1 mol) of 2,2-difluoro-1-methylcyclopropyl isocyanate in 100 ml oftoluene, and the mixture is stirred at room temperature for 16 hours.The reaction mixture is subsequently heated at 50° C. for another hour,and the solvent is then stripped off completely under reduced pressure 9g (63% of theory) of 2,2-difluoro-1-methyl-cyclopropylaminehydrochloride remain, in form of a solid substance of melting point140°-142° C. (decomposition).

EXAMPLE 11 ##STR50##

12 g (0.06 mol) of 20% strength aqueous sodium hydroxide solution areadded dropwise at 0° to 5° C. to a stirred mixture of 7.2 g (0.05 mol)of 2,2-difluoro-1-methyl-cyclopropylamine hydrochloride and 20 ml ofwater. The reaction mixture is extracted twice using diethyl ether, andthe combined organic phases are dried over magnesium sulphate andconcentrated under reduced pressure. The residue remaining is distilledoff under reduced pressure. In this manner, 3.9 g (73% of theory) of2,2-difluoro-1-methylcyclopropylamine are obtained in form of a liquidof boiling point 25°-30° C./15 mbar. Preparation of compounds of theformulae (V) or (XVII):

EXAMPLE 12 ##STR51##

A solution of 4.7 ml (0.09 mol) of bromine in 30 ml of methylenechloride is added dropwise to a stirred solution of 12.5 g (0.09 mol) of1-acetyl-1-methyl-2,2-difluoro-cyclopropane in 50 ml of methanol. Whendecoloration is complete, the reaction mixture is poured into 200 ml ofwater, and the mixture is extracted using methylene chloride. Afterconcentration under reduced pressure, 20 g (GC content 47%; 47% oftheory) of crude 1-bromoacetyl-1-methyl-2,2-difluorocyclopropane, whichis reacted directly without further purification, are obtained.##STR52##

6 g (0.028 mol) of 1-bromoacetyl-1-methyl-2,2-difluorocyclopropane arerefluxed for 16 hours and with stirring in 30 ml of acetone with theaddition of 4.4 g (0.032 mol) of potassium carbonate and 4.1 g (0.032mol) of 4-chlorophenol. The mixture is diluted with water, the productis extracted using methylene chloride, and the organic phase is washedonce with dilute sodium hydroxide solution and then with water, and thenconcentrated under reduced pressure.

6 g 1-(4-chlorophenoxyacetyl)-1-methyl-2,2-difluorocyclopropane areobtained as a crude product with a content (GC) of 66% (54.4% oftheory). ##STR53##

2.4 g (0.044 mol) of sodium methoxide are added to a solution of 30 ml(0.04 mol) of a 1.36-molar solution of trimethylsulphonium methylsulphate in acetonitrile, and the mixture is stirred for 30 minutes atroom temperature. 5.8 g (0.022 mol) of1-(4-chlorophenoxyacetyl)-1-methyl-2,2-difluorocyclopropane are thenadded, and the mixture is stirred for 16 hours at 20° C. The reactionmixture is poured into 200 ml of water, the mixture is extracted usingmethylene chloride, and the organic phase is washed with water andconcentrated.

4.3 g (GC purity of 73%; 71.6% of theory) of2-(4-chlorophenoxymethyl)-2-(2,2-difluoro-1-methylcyclopropyl)-oxiraneare obtained as a viscous resin which is reacted further directly.##STR54##

4.2 g (0.015 mol) of2-(4-chlorophenoxymethyl)-2-(2,2-difluoro-1-methylcyclopropyl)-oxirane,2.1 g (0.03 mol) of 1,2,4-triazole and 4.2 g (0.03 mol) of potassiumcarbonate are stirred in 30 ml of dimethylformamide for 16 hours at 90°C.

After the solvent has been removed on an oil pump, the residue isstirred with water/methylene chloride, and the organic phase isseparated off and concentrated. The residue is purified by means ofcolumn chromatography (chloroform/ethyl acetate=4:1) on silica gel.

2.3 g (44.6% of theory) of1-(4-chlorophenoxy)-2-(2,2-difluoro-1-methylcyclopropyl)-2-hydroxy-3-(1,2,4-triazol-1-yl)-propaneof melting point 110° C. are obtained.

EXAMPLE 13 ##STR55##

A solution of 15.5 g (0.11 mol) of p-chlorobenzaldehyde in 20 ml ofmethanol is added at 20° C. and with stirring to 15 g (0.11 mol) of1-acetyl-2,2-difluoro-1-methylcyclopropane in 20 ml of 10% strengthmethanolic sodium hydroxide solution. After 15 minutes, 40 ml more of10% strength methanolic sodium hydroxide solution are added, and themixture is stirred for 16 hours more at room temperature. The reactionmixture is poured into water, the mixture is extracted using methylenechloride, and the organic phase is washed with water and concentratedunder reduced pressure.

25 g (88% of theory) of crude 2,2-difluoro-1-methylcyclopropyl2-(4-chlorophenyl)-ethen-1-yl ketone are obtained as an oil which can bereacted further directly. ##STR56##

3.6 g (0.066 mol) of sodium methoxide are added to 41 ml (0.06 mol) of a1.46-molar solution of trimethylsulphonium methyl sulphate inacetonitrile, and the mixture is stirred for 30 minutes at roomtemperature. A solution of 10 g (0.039 mol)of(2,2-difluoro-1-methyl-cyclopropyl)[2-(4-chlorophenyl)-ethen-1-yl]ketone in 100 ml of acetonitrile is subsequently added, and the mixtureis stirred for 16 hours at room temperature. The reaction mixture isthen poured into water and extracted with methylene chloride, and theorganic phase is washed twice with water and concentrated under reducedpressure.

6.8 g (GC purity 38%; 24% of theory) of2-(2,2-difluoro-1-methylcyclopropyl)-2-[2-(4-chlorophenyl)-ethen-1-yl]-oxirane,which is reacted directly without further purification, are obtained.##STR57##

1.4 g (0.048 mol) of 80% strength sodium hydride are added in portionsto a solution of 3.3 g (0.048 mol) of 1,2,4-triazole in 30 ml ofdimethylformamide, and the mixture is stirred for 30 minutes at 20°-30°C. 6.6 g (0.024 mol) of2-(2,2-difluoro-1-methyl-cyclopropyl)-2-[2-(4-chlorophenyl)-ethen-1-yl]-oxiraneare subsequently added, and the mixture is stirred for 16 hours at 90°C. The reaction mixture is then poured into water, the mixture isextracted using methylene chloride, the organic phase is concentratedunder reduced pressure and the residue is purified by chromatography onsilica gel (chloroform/ethyl acetate=4:1).

2.4 g (29.6% of theory) of1-(4-chlorophenyl)-3-(2,2-difluoro-1-methylcyclopropyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)-but-1-eneof melting point 131° C. are obtained.

The substances of the formula (V) listed in the table below are alsoobtained following the methods indicated in Examples 12 and 13 andfollowing the processes disclosed in the description. ##STR58##

    ______________________________________                                        Exam- Com-                              Physical                              ple   pound                             constant                              No.   No.     Ar          Y        R    m.p. (°C.)                     ______________________________________                                        14    V-3                                                                                               OCH.sub.2                                                                              CH.sub.3                                                                           resin                                 15    V-4                                                                                    ##STR59##  OCH.sub.2                                                                              CH.sub.3                                                                           resin                                 16    V-5                                                                                    ##STR60##  CH.sub.2 CH.sub.2                                                                      CH.sub.3                                                                           112                                   17    V-6                                                                                    ##STR61##  OCH.sub.2                                                                              CH.sub.3                                                                           resin                                 18    V-7                                                                                    ##STR62##  OCH.sub.2                                                                              CH.sub.3                                                                           resin                                 19    V-8                                                                                    ##STR63##  OCH.sub.2                                                                              CH.sub.3                                                                           resin                                 ______________________________________                                    

EXAMPLE 20 ##STR64##

13.7 g (0.1% mol) of p-chlorophenyl-acetylene are added to a mixture of10.1 g (0.1 mol) of triethylamine, 1.4 g (0.01 mol) of copper(I) bromideand 55 ml of toluene, and the mixture is stirred for 30 minutes at roomtemperature under argon. After the reaction mixture has been heated to55° C., 15.5 g (0.1 mol) of 1-methyl-2,2-difluoro-cyclopropanecarbonylchloride are added dropwise. After this, the mixture is stirred for 8hours at 90° C., and then cooled and filtered. The filtrate is washed insuccession with dilute aqueous hydrochloric acid and water andconcentrated under reduced pressure. 19.2 g of a dark oil remain, whichis distilled using a bulb tube. At 0.1 mbar and a jacket temperature of120° C., a yellow oil passes over which solidifies on standing. 8.4 g(33% of theory) of 2-(4-chlorophenyl)-ethin-1-yl2,2-difluoro-1-methylcycloprop-1-yl ketone of melting point 67°-68° C.are obtained. ##STR65##

A mixture of 13 g of dimethyl sulphide and 4.8 g of dimethyl sulphate isinitially stirred for 2 hours at room temperature, and 18 ml oftert.-butanol and 8.9 g of 2-(4-chlorophenyl)-ethin-1-yl2,2-difluoro-1-methylcycloprop-1-yl ketone are then added. The mixtureis stirred for 30 minutes at room temperature and cooled to 10° C., anda solution of 4.5 g of potassium tert.-butoxide in 32 ml oftert.-butanol is then added in the course of one hour, with stirring.Stirring of the reaction mixture is continued for 3 hours at 10° C., andthe mixture is then concentrated by stripping off the diluent underreduced pressure. The residue is taken up in methylene chloride, washedthree times with water and dried, and is reconcentrated under reducedpressure. 6.4 g (68% of theory) of2-[2-(4-chlorophenyl)-ethin-1-yl]-2-(2,2-difluoro-1-methyl-cyclo-prop-1-yl)-oxiraneremain in the form of an oil which is reacted further without additionalpurification. ##STR66##

3,5 g of2-[2-(4-chlorophenyl)-ethin-1-yl]-2-(2,2-difluoro-1-methyl-cycloprop-1-yl)-oxiraneare added to a stirred mixture of 0.9 g (0.013 mol) of 1,2,4-triazole,1.8 g (0.013 mol) of ground potassium carbonate and 30 ml ofacetonitrile at room temperature. The mixture is refluxed for 8 hours,then cooled, diluted with water and extracted three times usingmethylene chloride. The combined organic phases are washed with water,then dried and concentrated under reduced pressure. In this manner, 3.8g of a dark oil are obtained which is purified by column chromatography(petroleum ether/ethyl acetate=2:1) on silica gel. 2.1 g (48% of theory)of1-(4-chlorophenyl)-3-(2,2-difluoro-1-methyl-cycloprop-1-yl)-4-(1,2,4-triazol-1-yl)-but-1-in-3-olremain in the form of a solid substance of melting point 113°-115° C.

In the following Use Examples, the compounds of the formulae indicatedbelow were employed as comparison substances: ##STR67##

EXAMPLE A

Erysiphe test (wheat)/protective

Solvent: 100 parts by weight of dimethylformamide

Emulsifier: 0.25 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dew-moist. After the spray coatinghas dried on, the plants are dusted with spores of Erysiphe graminisf.sp. tritici.

The plants are placed in a greenhouse at a temperature of about 20° C.and a relative atmospheric humidity of about 80%, in order to promotethe development of powdery mildew pustules.

Evaluation is carried out 7 days after the inoculation.

In this test, the compounds (V-1), (V-2), (V-3) and (V-4) show aconsiderably better activity than the comparison substances (B) and (C).

EXAMPLE B

Puccinia test (wheat)/protective

Solvent: 100 parts by weight of dimethylformamide

Emulsifier: 0.025 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are inoculated with aspore suspension of Puccinia recondita within a 0.1% strength aqueousagar solution. After the spore suspension has dried on, the plants aresprayed with the preparation of active compound until dew-moist. Theplants remain in an incubation cabin at 20° C. and 100% relativeatmospheric humidity for 24 hours.

The plants are placed in a greenhouse at a temperature of about 20° C.and a relative atmospheric humidity of about 80%, in order to promotethe development of rust pustules.

Evaluation is carried out 10 days after the inoculation.

In this test, the compounds (V-1), (V-2), (V-3), (V-4) and (V-5) show aconsiderably better activity than the comparison substance (A).

EXAMPLE C

Venturia test (apple)/protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dripping wet. After the spraycoating has dried on, the plants are inoculated with an aqueous conidiasuspension of the apple scab causative organism (Venturia inaequalis)and then remain in an incubation cabin at 20° C. and 100% relativeatmospheric humidity for 1 day.

The plants are then placed in a greenhouse at 20° C. and a relativeatmospheric humidity of about 70%.

Evaluation is carried out 12 days after the inoculation.

In this test, the compounds (V-1), (V-2) and (V-5) show a considerablybetter activity than the comparison substance (C).

EXAMPLE D

Erysiphe test (barley)/protective

Solvent: 100 parts by weight of dimethylformamide

Emulsifier: 0.25 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dew-moist. After the spray coatinghas dried on, the plants are dusted with spores of Erysiphe graminisf.sp. hordei.

The plants are placed in a greenhouse at a temperature of about 20° C.and a relative atmospheric humidity of about 80%, in order to promotethe development of powdery mildew pustules.

Evaluation is carried out 7 days after the inoculation.

In this test, the compound (XVII-1) shows a considerably better actionthan the comparison substance (D).

EXAMPLE E

Uromyces test (dwarf bean)/protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dripping wet. After the spraycoating has dried on, the plants are inoculated with an aqueousuredospore suspension of the bean rust causative organism (Uromycesappendiculatus) and remain in a dark humidity chamber at 20° to 22° C.and 100% relative atmospheric humidity for 1 day.

The plants are then placed in a greenhouse under intensive illuminationat 20° to 22° C. and a relative atmospheric humidity of 70 to 80% for 9days.

Evaluation is carried out 10 days after the inoculation.

In this test, the compound (XVII-1) shows a better activity than thecomparison substance (D).

EXAMPLE F

Pyricularia test (rice)/protective

Solvent: 12.5 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent, and theconcentrate is diluted with water and the stated amount of emulsifier,to the desired concentration.

To test for protective activity, young rice plants are sprayed with thepreparation of active compound until dripping wet. After the spraycoating has dried on, the plants are inoculated with an aqueous sporesuspension of Pyricularia oryzae. The plants are then placed in agreenhouse at 100% relative atmospheric humidity and 25° C.

Evaluation of the disease infestation is carried out 4 days after theinoculation.

In this test, the compound (XVII-1) shows a considerably better activitythan the comparison substance (D).

It will be appreciated that the instant specification and claims are setforth by way of illustration and not limitation, and that variousmodifications and changes may be made without departing from the spiritand scope of the present invention.

What is claimed is:
 1. A 2,2-difluorocyclopropyl derivative of theformula ##STR68## in which R¹ represents hydroxyl, methoxy or ethoxy. 2.A 2,2-difluorocyclopropyl derivatives according to claim 1, in whichsaid compound is 2,2-difluoro-1-methylcyclopropanecarboxylic acid of theformula ##STR69##